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irbesartan (Avapro)

Tradename: Avapro. Generic 2012 [8] * FDA issues recall(s) due to potential carcinogen N-nitrosodiethylamine (NDEA) [9] Indications: - treatment of hypertension, especially those who would benefit from an ACE inhibitor, but have had intolerable side effects - renal protection in patients with diabetes mellitus [5] - diabetic nephropathy - nondiabetic proteinuric nephropathy - chronic heart failure - left ventricular systolic dysfunction - left ventricular diastolic dysfunction [9] Contraindications: 1) pregnancy, trimesters 2 & 3, probably 1 as well 2) angioedema with ACE inhibitor 3) primary hyperaldosteronism 4) bilateral renal artery stenosis 5) biliary cirrhosis or biliary obstruction Dosage: 1) usual dose is 150 mg PO QD 2) 75 mg PO QD in volume or salt-depleted patients 3) max dose 300 mg QD; no benefit to larger doses 4) effect may be enhanced in combination with diuretic Tabs: 150, 300 mg Pharmacokinetics: 1) oral bioavailability is 60-80% 2) 90% is bound to plasma proteins 3) oxidized by cyt P450 2C9 4) elimination 1/2life is 11-15 hours 5) 20% of the drug is recovered in the urine 6) no dose adjustment for renal or hepatic insufficiency is necessary 7) volume of distribution 53-93 L Adverse effects: 1) similar to placebo [6] 2) fewer adverse effects than ACE inhibitors 3) cardiovascular - edema, chest pain, tachycardia 4) central nervous system - headache, dizziness, drowsiness, ataxia, insomnia, fatigue, anxiety, nervousness 5) gastrointestinal - diarrhea, abdominal pain, nausea, abnormal taste, dyspepsia, heartburn 6) hematologic: anemia, neutropenia 7) musculoskeletal - arthralgia, muscle cramps, myalgia 8) renal: polyuria, increased serum creatinine 9) respiratory - cough, upper respiratory tract infection, rhinitis, sinusitis, nasal congestion, pharyngitis 10) rash 11) increased liver function tests 12) decreased libido 13) serum K+ increases of > 20% in 4% of patients [6] 15) SciGen Pharmaceuticals has voluntary recalled ~1% of irbesartan, due presence of N-nitrosodiethylamine (NDEA), a probable human carcinogen Oct 2018 [9] Drug interactions: 1) any drug which inhibits cyt P450 2C9 can increase irbesartan levels: cimetidine 2) any drug which induces cyt P450 2C9 can diminish irbesartan levels: phenobarbital, ketoconazole 3) use caution with concurrent administration of K+ or K+-sparing diuretics Mechanism of action: 1) angiotensin II receptor antagonist 2) reduces progression of albuminuria in patients with diabetes mellitus type 2 [4]

Interactions

drug interactions drug adverse effects (more general classes) monitor with ARBs

Related

cytochrome P450 2C9; cytochrome P450 BP-1; cytochrome P450 MP-4; S-mephenytoin-4-hydroxylase; limonene 6-monooxygenase; limonene 7-monooxygenase (CYP2C9, CYP2C10)

General

angiotensin II receptor antagonist (ARB)

Properties

Database Correlations

PUBCHEM cid=3749

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 - not on National VA formulary
  3. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  4. Journal Watch 21(20):163, 2001 Parving H et al, NEJM 345:870, 2001
  5. Prescriber's Letter 9(11):61 2002
  6. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
  7. The ACTIVE I Investigators. Irbesartan in patients with atrial fibrillation. N Engl J Med 2011 Mar 10; 364:928. PMID: 21388310
  8. Prescriber's Letter 19(4): 2012 CHART: Anticipated Availability of First-Time Generics Detail-Document#: 280401 (subscription needed) http://www.prescribersletter.com
  9. Brooks M FDA Issues Alert on Irbesartan Due to Contamination. Medscape - Nov 01, 2018. https://www.medscape.com/viewarticle/904270 - FDA Safety Alert. Jan 3, 2019 FDA updates on angiotensin II receptor blocker (ARB) recalls including valsartan, losartan and irbesartan. https://www.fda.gov/drugs/drugsafety/ucm613916.htm

Component-of

hydrochlorothiazide/irbesartan (Avalide)